Patent RU-2276151-C2 (RU)
Inventor: EHNNEKEN LORAN FRANSUA ANDRE
IPC: A61P35/00
Filed: 2001-06-01
Granted: 2006-05-10
Abstract: FIELD: organic chemistry, medicine, oncology, pharmacy. 
     SUBSTANCE: invention relates to quinazoline derivatives of the formula (I)   or their pharmaceutically acceptable salts wherein m = 0 or 1; each group R 1  can be similar or different and represents halogen atom, hydroxy- and (C 1 -C 6 )-alkoxy-group, or group of the formula Q 3 -X 1  wherein X 1  represents oxygen atom (O); Q 3  represents phenyl-(C 1 -C 6 )-alkyl, heteroaryl-(C 1 -C 6 )-alkyl, heterocyclyl or heterocyclyl-(C 1 -C 6 )-alkyl, and wherein heteroaryl group represents aromatic 5- or 6-membered monocyclic rings with one or two nitrogen heteroatoms, and any heterocyclyl group defined as the group R 1  represents non-aromatic saturated or partially saturated 3-6-membered monocyclic ring with one or two heteroatoms chosen from oxygen and nitrogen atoms, and wherein adjacent carbon atoms in any (C 2 -C 6 )-alkylene chain in the substitute R 1  are separated optionally by incorporation of oxygen atom (O) in the chain, and wherein any group CH 2  or CH 3  in the substitute R 1  comprises optionally in each of indicated groups CH 2  or CH 3  one or some halogen substitutes or a substitute chosen from hydroxy-, (C 1 -C 6 )-alkoxy-group, (C 1 -C 6 )-alkylsulfonyl or pyridyloxy-group, and wherein any heteroaryl or heterocyclyl group in the substitute R 1  comprises optionally 1, 2 or 3 substitutes that can be similar or different and chosen from hydroxy-group, carbamoyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxycarbonyl, N-(C 1 -C 6 )-alkylcarbamoyl, N,N-di-[(C 1 -C 6 )-alkyl]-carbamoyl, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl and cyano-(C 1 -C 6 )-alkyl, or among  group of the formula -X 5 -Q 6  wherein X 5  represents a direct bond or -CO, and Q 6  represents heterocyclyl or heterocyclyl-(C 1 -C 6 )-alkyl that comprises optionally (C 1 -C 6 )-alkyl as a substitute wherein heterocyclyl group represents non-aromatic, fully or partially saturated 5- or 6-membered monocyclic ring with one or two heteroatoms chosen from nitrogen and oxygen atom; R 2  represents hydrogen atom; R 3  represents hydrogen atom; Z represents a direct bond or oxygen atom; Q 1  represents phenyl, (C 3 -C 7 )-cycloalkyl, heteroaryl-(C 1 -C 6 )-alkyl, heterocyclyl or heterocyclyl-(C 1 -C 6 )-alkyl wherein heteroaryl group represents 5- or 6-membered aromatic monocyclic ring with I, 2 or 3 heteroatoms of nitrogen, and any heterocyclyl group represents non-aromatic fully or partially saturated 5- or 6-membered monocyclic ring with one or two heteroatoms chosen from oxygen, nitrogen or sulfur atom, or when Z represents oxygen atom (O) then Q 1  can represent (C 1 -C 6 )-alkyl or (C 1- C 6 )-alkoxy-(C 1 -C 6 )-alkyl and wherein any heterocyclyl group in the group -Q 1 -Z- comprises substitutes chosen from (C 1 -C 6 )-alkyl, (C 1 -C)-alkoxycarbonyl and pyridylmethyl, and wherein any heterocyclyl group in the group -Q 1 -Z- comprises optionally 1 or 2 oxo-substitutes; Q 2  represents aryl group of the formula (Ia):   wherein G 1  represents halogen atom, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl, (C 2 -C 8 )-alkynyl, (C 1 -C 6 )-alkoxy-, (C 1 -C 6 )-alkylthio-group, (C 2 -C 6 )-alkanoyl, pyrrolyl, pyrrolidinyl, piperidinyl and morpholinomethyl, and each G 2 , G 3 , G 4  and G 5  that can be similar or different represents hydrogen, halogen atom, cyano-group, (C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl, (C 2 -C 8 )-alkynyl and (C 1 -C 6 )-alkoxy-group, or G 1  and G 2  form in common group of formulae -CH=CH-CH=CH-, -CH=CH-O- or -O-CH=CH- being each group carries optionally halogen atom as a substitute, or G 1  and G 2  form in common group of formulae -O-CH 2 -O- or -O-CH 2 -CH 2 -O-, or -O-CH 2 -CH 2 -O-, and each among G 3  and G 4  represents hydrogen atom, and G 5  is chosen from hydrogen and halogen atom. Proposed compounds possess anti-tumor activity and designated for preparing a medicine preparation for its using as an anti-tumor agent for suppression and/or treatment of solid tumors. Also, invention relates to a pharmaceutical composition based on abovementioned compounds. 
     EFFECT: valuable medicinal properties of compounds. 
     20 cl, 7 tbl, 57 ex